Vaccines are often referred to as biologicals or biological products. This is because they may be prepared by cultivation of live micro-organisms using live tissue cells of animal origin as a substrate. Moreover the culture media are often supplemented with specific substances of animal origin, notably serum, to achieve a satisfactory growth of the micro-organisms. Also in the production process itself, substances of animal origin are often used, such as in a stabilizer. Consequently there exists a potential risk that vaccines may become contaminated with extraneous “animal origin” agents.
Often, a vaccine is mixed with stabilizers, e.g. to protect degradation-prone components from being degraded, to enhance the shelf-life of the vaccine, or to improve freeze-drying efficiency. Useful stabilizers are i.a. SPGA (Bovarnik et al., 1950, J. Bacteriology, vol. 59, p. 509), skimmed milk, gelatine, bovine serum albumin, carbohydrates e.g. sorbitol, mannitol, trehalose, starch, sucrose, dextran or glucose, proteins such as albumin or casein or degradation products thereof, and buffers, such as alkali metal phosphates. These stabilizers are a source of “animal origin” agents/components.
The prior art has identified the need for the production of biological materials that are free from contamination, such as “animal origin” contamination. Biological materials are often subjected to numerous tests and/or evaluations to illustrate that the materials are free from contamination. Accordingly, production of a vaccine or immunogenic composition with a stabilizer containing animal origin components is, in itself, a source of contamination.
Such animal origin components often require extra precautions such as filter sterilization, and present difficulties, such as batch to batch variability of a vaccine, and the like. In fact, vaccines grown in a serum free culture are often mixed with stabilizers of animal origin, thereby producing a vaccine which is no longer free of animal origin components.
Accordingly, the art field desires stabilizer that is free from animal origin components. An animal origin free stabilizer would be sterilizable by autoclaving. An animal origin free stabilizer (a Non-Animal Origin (NAO) Stabilizer) would not suffer complicating batch to batch variability of animal compounds. However, and most importantly an animal origin free stabilizer would allow an animal origin free vaccine, as up to now serum-free culturing already reduced the risk of extraneous agents in the animal compounds, however those products were still freeze dried with compounds of animal origin, thereby re-introducing a risk of contamination.
Examples of prior art documents that show the state of the art prior to Applicants' invention comprise: WO 93/18790, and U.S. Pat. Nos. 5,948,411; 6,039,958; and, 6,258,362